Pertussis, more commonly known as whooping cough, is a contagious disease caused by the bacteria Bordetella pertussis attaching to the cilia that line the upper respiratory tract and making airway swell [6]. Pertussis is spread through the inhalation of droplets from sneezing or coughing infected individuals [4] and has an incubation period of seven to ten days [8]. While occurrences have declined since the introduction of the vaccine in 1940s, every three to five years there is a spike in incidences reported (see Figure 1) [5]. Pertussis remains a significant contributor to infant death, especially for infants who are not fully vaccinated [6]. For infants under the age of one, pertussis can lead to a number of complications including pneumonia, convulsions, apnea, encephalopathy, and as many as one death in every one hundred cases or more if you factor in deaths from the complications that arise [6]. Early treatment with antibiotics is important and can make the infection less serious [6].
Figure 1. Reported cases of pertussis in the U.S. by age group from 1990 to 2010.
References:
Baće, A.; Zrnić, T.; Begovac, J.; Kuzmanović, N.; Culig, J., Short-term treatment of pertussis with azithromycin in infants and young children. Eur J Clin Microbiol Infect Dis 1999,18 (4), 296-8.
Bakheit, A. H.; Al-Hadiya, B. M.; Abd-Elgalil, A. A., Azithromycin. Profiles Drug Subst Excip Relat Methodol 2014,39, 1-40.
Hansen, J. L.; Ippolito, J. A.; Ban, N.; Nissen, P.; Moore, P. B.; Steitz, T. A., The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell 2002,10 (1), 117-28.
Kannan, K.; Mankin, A. S., Macrolide antibiotics in the ribosome exit tunnel: species-specific binding and action. Ann N Y Acad Sci 2011,1241, 33-47.
Leber, A. L., Pertussis: relevant species and diagnostic update. Clin Lab Med 2014,34 (2), 237-55.
Silvers, J. A.; Champney, W. S., Accumulation and turnover of 23S ribosomal RNA in azithromycin-inhibited ribonuclease mutant strains of Escherichia coli. Arch Microbiol 2005,184 (1), 66-77.
Spector, T. B.; Maziarz, E. K., Pertussis. Med Clin North Am 2013,97 (4), 537-52, ix.
Figure 2. The large ribosomal subunit labeled with the macrolide binding position shown and boxed [3].
Size: ~1.3×106 Da
Location: Large ribosomal subunit 50S in the prokaryotic ribosome 70S
Function in a normal cell: In a normal cell, the 50S ribosomal promotes the peptidyl transfer and prevents peptidyl hydrolysis as well as helps protein formation.
Drug Information: Azithromycin
Schematic figure of drug:
Figure 3. Structural formula of azithromycin hydrate [2].
Formula: C38H72N2O12H2O Molecular weight: 767.02 g CAS Number: 121479-24-4
Delivery method: Oral pill or injection Side effects: Anorexia, dyspepsia, flatulence, dizziness, headache, drowsiness, convulsions, arthralgia, and disturbances in taste and smell and rarely constipation, hepatitis, hepatic failure, syncope, insomnia, agitation, anxiety, asthenia, paraesthesia, hyperactivity, thrombocytopenia, haemolytic anaemia, interstitial nephritis, acute renal failure, photosensitivity, tooth and tongue discoloration
Other names:Zithromax, AzaSite, and Zmax
Maker or company: Pfizer
Is it patented? Yes, by Pliva in 1981
Clinical Trials Info: A study investigating the use of azithromycin to treat pertussis in infants was performed in 1999. The study found that in infants ages two to eighteen months 3 day and 5 day courses of azithromycin were successfully able to eradicate the Bordetella pertussis by day fourteen [1]. In addition, azithromycin was well tolerated, with no gastrointestinal symptoms such as abdominal pain, loose stool, or diarrhea, which had been a problem for other macrolide antibiotics such as erythromycin and clarithromycin [1, 6]
Origin: Azithromycin is a synthetic macrolide derived from erythromycin.
Alternatives to this drug: Erythromycin or clarithromycin Miscellaneous: Other uses: Azithromycin can be used to treat a variety of diseases including ischaemic heart disease, gingival hyperplasia, and cystic fibrosis [2].
Disease/Drug of interest: Pertussis
Motivation and Background:
Pertussis, more commonly known as whooping cough, is a contagious disease caused by the bacteria Bordetella pertussis attaching to the cilia that line the upper respiratory tract and making airway swell [6]. Pertussis is spread through the inhalation of droplets from sneezing or coughing infected individuals [4] and has an incubation period of seven to ten days [8]. While occurrences have declined since the introduction of the vaccine in 1940s, every three to five years there is a spike in incidences reported (see Figure 1) [5]. Pertussis remains a significant contributor to infant death, especially for infants who are not fully vaccinated [6]. For infants under the age of one, pertussis can lead to a number of complications including pneumonia, convulsions, apnea, encephalopathy, and as many as one death in every one hundred cases or more if you factor in deaths from the complications that arise [6]. Early treatment with antibiotics is important and can make the infection less serious [6].Figure 1. Reported cases of pertussis in the U.S. by age group from 1990 to 2010.
References:
External links:
Government CDC website on pertussis: https://www.cdc.gov/pertussis/Target Information: 50S Ribosomal Unit
Figure 2. The large ribosomal subunit labeled with the macrolide binding position shown and boxed [3].
Size: ~1.3×106 Da
Location: Large ribosomal subunit 50S in the prokaryotic ribosome 70S
Function in a normal cell: In a normal cell, the 50S ribosomal promotes the peptidyl transfer and prevents peptidyl hydrolysis as well as helps protein formation.
Drug Information: Azithromycin
Schematic figure of drug:
Figure 3. Structural formula of azithromycin hydrate [2].
Formula: C38H72N2O12H2O
Molecular weight: 767.02 g
CAS Number: 121479-24-4
Delivery method: Oral pill or injection
Side effects: Anorexia, dyspepsia, flatulence, dizziness, headache, drowsiness, convulsions, arthralgia, and disturbances in taste and smell and rarely constipation, hepatitis, hepatic failure, syncope, insomnia, agitation, anxiety, asthenia, paraesthesia, hyperactivity, thrombocytopenia, haemolytic anaemia, interstitial nephritis, acute renal failure, photosensitivity, tooth and tongue discoloration
Other names: Zithromax, AzaSite, and Zmax
Maker or company: PfizerIs it patented? Yes, by Pliva in 1981
Clinical Trials Info: A study investigating the use of azithromycin to treat pertussis in infants was performed in 1999. The study found that in infants ages two to eighteen months 3 day and 5 day courses of azithromycin were successfully able to eradicate the Bordetella pertussis by day fourteen [1]. In addition, azithromycin was well tolerated, with no gastrointestinal symptoms such as abdominal pain, loose stool, or diarrhea, which had been a problem for other macrolide antibiotics such as erythromycin and clarithromycin [1, 6]Origin: Azithromycin is a synthetic macrolide derived from erythromycin.
Alternatives to this drug: Erythromycin or clarithromycin
Miscellaneous:
Other uses: Azithromycin can be used to treat a variety of diseases including ischaemic heart disease, gingival hyperplasia, and cystic fibrosis [2].